Seizures phenobarbital

Convulsions associated with fever often occur in children 3 months to 5 years of age. Epilepsy later develops in approximately 2 to 3% of children who exhibit one or more such febrile seizures. Most authorities now recommend prophylactic treatment with anticonvulsant drugs only to patients at highest risk for development of epilepsy and for those who have multiple recurrent febrile seizures. Phenobarbital is the usual drug, although diazepam is also effective. Phenytoin and carba-mazepine are ineffective, and valproic acid may cause hepatotoxicity in very young patients. 

Barbiturates are also used in infantile seizures that are not considered epilepsy. These seizures generally occur when an infant has a high fever, and therefore they are called febrile seizures. Phenobarbital is still commonly used to prevent seizures in infants, because scientists do not routinely study new drugs in infants and children. Because phenobarbital is... 

To date, among the newer-generation agents, only lamotrigine and oxcarbazepine have received Food and Drug Administration (FDA) approval for use as monotherapy in patients with partial seizures. Phenobarbital and primidone are also useful in partial... 

Epilepsy is a disease that is characterized by recurring convulsive seizures. Phenobarbital, 58, possess specific usefulness in epilepsy. In general, barbituric acid derivatives are synthesized from phenylethyl-malonic diethyl ester [8]. 

Primidone [125-33-7] C22H24N2O2 (39) is an analogue of phenobarbital that is used for the treatment of generalized tonic-clonic seizures. It is metabolized in humans to phenobarbital (6) and phenylethyLmalondiamide [7206-76-0J, C22H24N2O2 (40) and these metaboUtes are probably responsible for its anticonvulsant actions. Primidone has many of the side effect HabiUties seen with phenobarbital. 

Occasionally, status epilepticus (an emergency situation characterized by continual seizure activity with no interruptions) can occur. Diazepam (Valium) is most often the initial drug prescribed for this condition. However, because the effects of diazepam last less than 1 hour, a longer-lasting anticonvulsant, such as phenytoin or phenobarbital, also must be given to control the seizure activity. 

The most common adverse reaction associated with phenobarbital is sedation, which can range from mild sleepiness or drowsiness to somnolence. These dru > may also cause nausea, vomiting, constipation, bradycardia, hypoventilation, skin rash, headache fever, and diarrhea Agitation, rather than sedation, may occur in some patients. Some of these adverse effects may be reduced or eliminated as therapy continues. Occasionally, a slight dosage reduction, without reducing the ability of the drug to control the seizures, will reduce or eliminate some of these adverse reactions. 

Anticonvulsant drugs such as carbamazepine, diazepam, valproic acid, and phenobarbital also slightly increased the duration of the initial AD. However, the effects of these drugs on the other associated seizure events were quite different from PCP and ketamine. The effects of carbamazepine and diazepam, typical of the four compounds, are illustrated in figure 4. These compounds either suppressed the rebound spiking (diazepam, valproic acid, and phenobarbital) or lengthened the total seizure duration with no rebound suppression (carbamazepine). 

The results demonstrate anticonvulsant properties of PCP and ketamine in two quite different seizure models. On the one hand, ketamine was effective in antagonizing several components of PTZ activity. Others have previously reported anti-PTZ effects of ketamine. However, the present results demonstrate that the anticonvulsant effects of ketamine against PTZ seizures closely resembled the effects of phenobarbital in that both compounds delayed clonic convulsions and prevented tonic extension. Moreover, a low dose of ketamine, which alone showed no anticonvulsant effect or overt behavioral changes, potentiated the anti-PTZ effects of phenobarbita 1. These findings suggest that ketamine possesses selective anticonvulsant properties. The anticonvulsant mechanism of action for phenobarbital is not known. However, the similarities between ketamine and phenobarbital, and the interaction between the two compounds, suggest a common mechanism or site of acti on. 

The consultant pharmacist is reviewing the care of AN, who is a 79-year-old male resident of a long-term care facility. According to his records, he has received phenytoin and phenobarbital ever since suffering a stroke 12 years ago. There is no record of a seizure in his chart, and the nursing staff has not observed a seizure since he arrived at the facility 2 years ago. His family recalls that he had 1 seizure around the time of his stroke, but has not had any more seizures. 

Acute management of toxaphene-induced seizures in humans with anticonvulsants, especially diazepam, phenobarbital, and phenytoin (USPHS 1994). 

Phenobarbital is the drug of choice for neonatal seizures, but in other situations it is reserved for patients who have failed other AEDs. 

Once seizures are terminated, dosages can be decreased by 1 mcg/kg/min every 2 hours. Successful discontinuation is enhanced by maintaining serum phenytoin concentrations above 20 mg/L and phenobarbital concentrations above 40 mg/L. 

Following acute exposure to cyclodiene organochlorine pesticides, seizures and respiratory depression may occur (Ellenhom 1988 Proctor et al. 1988). Benzodiazepines (e.g., diazepam or lorazepam) or other anticonvulsant medications (e.g., phenobarbital) have been commonly used to control seizures (Ford 1993). Organochlorines may sensitize the myocardium to the proarrhythmic effects of adrenergic amines, potentially resulting in initiation of ventricular fibrillation (TOMES 1994). 

Barbiturates. The first barbiturate, barbital, was introduced at the turn of the 20th century. Hundreds of others, including phenobarbital and pentobarbital, were later developed. The barbiturates were a highly successful class of medications as it became clear that they treated not only alcohol withdrawal but seizure disorders, anxiety, and insomnia as well. By the 1960s, however, the barbiturates were largely surpassed by the benzodiazepines. The newer benzodiazepines act in a similar fashion and provide much the same therapeutic benefit but are significantly safer and easier to tolerate. 

Anticonvulsant (mephobarbital, phenobarbital) Treatment of partial and generalized tonic-clonic and cortical focal seizures. 

Epilepsy, monotherapy Indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). 

Seizures. Simple isolated seizures may require only observation and supportive care. Repetitive seizures or status epilepticus require therapy. Give IV diazepam or lorazepam followed by fosphenytoin and/or phenobarbital. Pancuronium may also be considered. 

Exposed individuals with evidence of central nervous system depression or seizures should be evaluated for the presence of some other underlying disorder. Diazepam or phenobarbital may be administered to alleviate seizures. Supplemental oxygen can also be administered. If pulmonary edema occurs, conventional therapy should be considered. Additional information regarding the treatment of individuals exposed to cresols may be obtained from Bronstein and Currance (1988), Haddad and Winchester (1990), and Stutz and Janusz (1988). 

With some drugs, particularly those with a long half life, a loading dose may be useful in order to achieve a therapeutic level more rapidly. For example, the half-life of phenobarbital in the neonate is long, approximately 120 hours, with steady-state concentrations achieved in two to three weeks. A slowly-infused loading dose can be efficacious in achieving seizure control within minutes, typically followed by maintenance infusion and subsequent transition to oral therapy daily. 

Phenobarbital is still used for the management of partial seizures, generalized tonic-clonic seizures and for the control of status epilepticus. However because of its low therapeutic index and the possibility of dependence, phenobarbital has largely been displaced by other anticonvulsants. For newborns phenobarbital is often the drug of first choice. If given together with sodium valproate the metabolism of phenobarbital may be inhibited while in combination with carbamazepine the serum concentrations of carbamazepine will be reduced due to enzyme induction by phenobarbital. 

Primidone is an other second line barbiturate used orally to control tonic-clonic and partial seizures. It is a pro-drug as it is metabolized to phenobarbital and phenylethylmalonamide (PEMA), however both the parent compound as well as the metabolites have anti seizure activity. Its use is more difficult to monitor and adverse effects occur even more frequently than with phenobarbital. 

Conversely, certain drugs modify the effectiveness or side effects of aspirin. Phenobarbital, occasionally used for seizures, induces liver enzymes that increase the metabolism and excretion of aspirin, (3-adrenoceptorblocking drugs, such as propranolol, and decrease the antiinflammatory effects of aspirin, whereas reserpine decreases its analgesic effects. Antacids decrease the absorption of aspirin. Alcohol consumption in combination with aspirin increases the latter s ulcerogenic effects. 

The first effective treatment of seizure disorders was the serendipitous finding in 1857 that potassium bromide could control seizures in some patients. Even though side effects were troublesome, the bromides were widely used for many years. Phenobarbital was introduced as a treatment for epilepsy in 1912 and was immediately shown to be markedly superior to bromides. While other barbiturates were synthesized and used, none were shown to be superior to phenobarbital, and the latter compound is still used. A chemically related... 

Phenobarbital and primidone are quite similar both chemically and pharmacologically, and much of the anticonvulsant activity of primidone may be ascribed to its metabolic conversion to phenobarbital. As would be expected in such a case, the clinical indications for the two compounds are very similar. There is some indication that primidone may be more effective in the treatment of partial seizures with complex symptoms, but the evidence is not compelling. 

At present, phenobarbital and primidone are considered as alternative drugs for the treatment of partial seizures and for generalized tonic-clonic epilepsy. They are judged to be less effective than carbamazepine and phenytoin. 

Serum phenobarbital concentration (therapeutic range for seizure disorders 20-40 mcg/ml)... 

Second-line anticonvulsant for treatment of generalized tonic-clonic seizures (or alternative to phenobarbital, which probably accounts for most of the anticonvulsant activity)... 

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